Association between cadmium concentration in rice and mortality in the Jinzu River basin, Japan

doi:10.1016/S0300-483X(01)00367-5

Toxicology

Volume 163, Issue 1, 28 May 2001, Pages 23-28

https://doi.org/10.1016/S0300-483X(01)00367-5 Get rights and content

Abstract

A follow-up survey on 2101 inhabitants (1566 men, 535 women), who participated in a 1967 health survey and had resided in their present rural community since birth was conducted to determine the influence of environmental cadmium exposure on the mortality of the general population in the Jinzu River basin. The survey was conducted over 6128 days from August 1, 1967 to May 10, 1984. The rural communities were divided into two groups, one with a cadmium concentration in rice of <0.30 ppm and the other ≥0.30 ppm. The influence of cadmium concentration in rice on mortality was analyzed using SMRs and a Cox's proportional hazards model. In both sexes, SMRs tended to be greater in the ≥0.3 ppm group as compared to <0.3 ppm group. The Cox hazard ratios for males and females in the ≥0.30 ppm group, to those in the <0.30 ppm group, were 1.42 and 1.10, respectively (significant in the men). Since the mean cadmium concentration in rice in each rural community was closely related to the development of renal injury, in regions with high cadmium concentrations in rice, the development of renal injury induced by cadmium is believed to be the factor underlying the increased mortality observed.

Introduction

Widespread contamination of rice with cadmium (Cd) from an upstream zinc mine contributed to numerous cases of Itai-itai disease along the Jinzu River basin in the Toyama Prefecture of Japan, during and after World War II. This syndrome involves severe bone pain, spontaneous fractures, and renal, particularly renal tubular injury (Nogawa et al., 1980, Nogawa, 1981). Renal injury was also observed in a high proportion of the exposed population in this area.

Shigematsu conducted a 30-year survival survey and investigated the relationship between environmental Cd exposure and mortality in this region. He classified regions into three groups according to Cd concentrations in unpolished rice. Based on SMRs calculated in each region, all cases of death in both sexes were found to be significantly lower in the polluted as compared to the non-polluted regions, with similar results obtained when the mortality rates were observed according to the degree of pollution present (Shigematsu, 1980, Shigematsu, 1982). On the other hand, in 1990, Nakagawa et al. reported that Itai-itai disease patients and subjects with suspected disease showed higher mortality and shorter life spans as compared with control subjects (Nakagawa et al., 1990). Only these two studies have focused on the influence of Cd exposure on mortality in the Jinzu River basin, with no consensus reached on this issue as of yet.

According to the studies of Tsuchiya and Iwao, the inhabitants of Cd-polluted districts in Japan derive one-half to two-thirds of their total Cd intake from rice (Tsuchiya and Iwao, 1978). Thus, it would be useful to understand the relationship between Cd concentration in rice and mortality when investigating the influence of Cd exposure in the general environment on mortality. We therefore undertook the present study to elucidate the relationship between environmental Cd exposure and mortality in inhabitants of the Jinzu River basin using the Cd concentrations in rice as an index of Cd exposure.

Section snippets

Study population

In 1967 and 1968, large-scale health examinations were conducted among the entire population aged ≥30 years of the Jinzu River basin, non-Jinzu River basin, and a region receiving a mixed water supply from the two sources. Subjects for the present study were selected from among the 6667 participants (3181 men, 3486 women, participation rate 93.4%) who took part in the 1967 health survey, which was conducted mainly in the heavily polluted region. Of these, 2101 inhabitants (1566 men, 535 women)

Results

The number of subjects at the beginning of the observation period, number of subjects followed up completely during the observation period, number of deaths during this period, mean number of observed person-days, mean age, and mean Cd concentration in rice are listed in Table 1. Prevalences of proteinuria, glucosuria and proteinuria with glucosuria are shown in the same table for reference.

The mortality rate per 1000 person-years was significantly higher in the ≥0.30 ppm group, compared with

Discussion

Two types of dose estimates can be used in investigations of the dose–response relationship — namely, an external or internal dose. In the case of environmentally exposed Japanese populations, the concentration of Cd in rice is generally used as the external dose, as rice is the main source of Cd intake in most Cd-polluted areas (Tsuchiya and Iwao, 1978). A number of studies have been carried out using the mean concentration of Cd in rice from individual rural communities or total Cd intake

References (18)

K. Aoshima et al.
Evaluation of qualitative and qualitative tests for proteinuria and glucosuria as screening tests for cadmium-induced renal tubular dysfunction
Jpn. J. Hyg.
(1990)
Y. Hochi et al.
Dose–response relationship between total cadmium intake and prevalence of renal dysfunction using general linear models
J. Appl. Toxicol.
(1995)
T. Izuno et al.
Validity of cadmium concentration in rice as the ‘dose’ of the dose–response relationship between cadmium intake and renal dysfunction
Environ. Res.
(2000)
L. Jarup et al.
Health effects of cadmium exposure — a review of the literature and a risk estimate
Scand. J. Work Environ. Health
(1998)
Kawano, S., 1976. A study on the relationships between rice-cadmium concentrations and health effects. In: Results of...
T. Kido et al.
Dose–response relationship between total cadmium intake and β₂-microglobulinuria using logistic regression analysis
Toxicology
(1993)
T. Kido et al.
Dose–response relationship between dietary cadmium intake and metallothioneinuria in a population from a cadmium-polluted area of Japan
Toxicology
(1991)
T. Kido et al.
Dose–response relationship between dietary cadmium intake and metallothioneinuria using logistic regression analysis
Toxicology
(1993)
H. Nakagawa et al.
High mortality and shortened life-span in patients with Itai-itai disease and subjects with suspected disease
Arch. Environ. Health
(1990)

There are more references available in the full text version of this article.

Cited by (52)

Cadmium
2021, Handbook on the Toxicology of Metals: Fifth Edition
Cadmium (Cd) occurs with zinc and lead in sulfide ores. Elevated concentrations in air, water, and soil may occur close to nonferrous mining and metal refining industries. Cadmium metal has been used as an anticorrosive when electroplated onto steel. Cd compounds are used in batteries, as pigments and in solar panels. Between 10% and 50% of inhaled Cd will be absorbed and 5%–10% of ingested Cd. The accumulation of Cd in humans occurs in many tissues, with particularly long half-lives (10–30 years) in muscle, bone, kidney, and liver. Cd bound to metallothionein in plasma is filtered through the renal glomeruli and reabsorbed in the tubuli, where the metal ion is released and toxic effects occur. The average amount of Cd ingested in Japan and most European and North American countries is <10–20 μg/day. The corresponding average urinary excretion of Cd is <0.5–1.0 μg/day and the blood concentration is 0.2–0.7 μg/L in nonsmokers; it is twice as high in smokers. Acute inhalation of Cd in air, for example, from soldering or welding fumes, may lead to severe chemical pneumonitis. Long-term exposure to low air levels may lead to chronic obstructive lung disease and possibly to lung cancer. Long-term excessive exposure from the air or food leads to renal tubular dysfunction with low molecular weight proteinuria. It may also lead to disturbance of calcium metabolism, osteoporosis, and osteomalacia, mainly among postmenopausal women. A disease exhibiting these features—called itai-itai disease—occurred in the 1950s in a Cd-polluted area of Japan. Cd-induced cancer of the lungs, prostate, and other organs in animals and increased rates of cancer of the lungs and other organs in humans. The International Agency for Research on Cancer (IARC) classified Cd as a human carcinogen (Group 1). Adverse kidney effects occur in sensitive occupational groups, as well as in general population groups, after lifelong exposures giving rise to urinary Cd (UCd) of 2–4 μg/g creatinine. At such exposures, bone effects including osteoporosis and fractures may also occur in sensitive groups. Adverse bone and kidney effects may occur in a small but sensitive population group as a result of lifelong cadmium exposure with UCd of approximately 1 μg/g creatinine and higher, but the evidence is still inconclusive. This level of exposure occurs within general population groups in many countries. Osteomalacia is treated with large doses of vitamin D, but there is no effective treatment for other Cd-related effects. Because of the long half-life of Cd and the irreversibility of bone effects and some kidney effects, primary prevention is essential. The toxicological and environmental aspects of Cd have been reviewed in detail by Friberg et al. (1974, 1985, 1986), Tsuchiya (1978), Nriagu (1980, 1981), the WHO/IPCS (1992), the IARC (1993, 2012), Järup et al. (1998c), the Agency for Toxic Substances and Disease Registry (ATSDR, 1999), Nordberg and Nordberg (2002), the European Union (EU, 2003, 2007; ECHA 2020), Satarug and Moore (2004), and the World Health Organization Food and Agriculture Organization (JECFA, 2004, 2012), the European Food Safety Authority (EFSA, 2009, 2012), Akesson et al. (2014), the Scientific Committee on Occupational Exposure Limits (SCOEL, 2017), and the International Union of Pure and Applied Chemistry (Nordberg et al., 2018).
Contribution of arbuscular mycorrhizal fungi in promoting cadmium tolerance in plants
2019, Cadmium Tolerance in Plants: Agronomic, Molecular, Signaling, and Omic Approaches
Cadmium (Cd) is the most hazardous heavy metal element to organisms. Cd can induce oxidative stress in plants that disrupts cellular homeostasis, damages proteins and pigments, and leads to lipid peroxidation. Although plant metabolism has some response mechanisms to Cd stress, in highly contaminated sites the development of these mechanisms is compromised. Under such conditions, mycorrhizal symbiosis can increase Cd tolerance using various mechanisms. This symbiosis can reduce Cd uptake by plants and thus reduce Cd stress. In addition, the increased activity of antioxidant defense system enzymes and secondary metabolite production related to plant defense have been widely reported in mycorrhizal plants. At the molecular level, mycorrhizal colonization alters the gene expression of several metal transporters, providing greater adaptability of plants in Cd-contaminated areas. Therefore, the use of mycorrhiza in phytoremediation programs constitutes a promising and beneficial technique for ecosystems through the agronomic management of indigenous and exogenous arbuscular mycorrhizal fungi.
Increase of lifetime cadmium intake dose-dependently increased all cause of mortality in female inhabitants of the cadmium-polluted Jinzu River basin, Toyama, Japan
2018, Environmental Research
Citation Excerpt :
U-Cd has been recognized as a potential marker for the total body burden of Cd exposure (Järup and Åkesson, 2009). Moreover, a significant association was observed between an external index of Cd-exposure, that is, Cd concentration in rice and mortality (Ishihara et al., 2001). Previous epidemiological studies in Japan indicated that Cd from rice accounted for 30–40% of the daily Cd intake in non-polluted areas (Ikeda et al., 2004; Watanabe et al., 2000), while a higher contribution of up to 70% was observed in some polluted areas (Ikeda et al., 2004; Tsuchiya and Iwao, 1978).
Exposure to cadmium (Cd) via food is supposed to affect life prognosis of inhabitants of Cd-polluted area in Japan. However, there have been few reports demonstrating a significant relationship between the amount of Cd intake and mortality. We aimed to investigate the relationship between mortality and individual lifetime Cd intake (LCd) in inhabitants of the polluted Jinzu River basin, Toyama, Japan.
We conducted a 26-year follow-up survey in 2407 inhabitants (1208 men and 1199 women) who participated in health examinations for screening of renal dysfunction from 1979 to 1984. The calculation of LCd in each inhabitant was based on the formula of Nogawa (Nogawa et al., 1989): (mean Cd concentration in rice of the present hamlet × 333.5 g/day + 34 μg/day) × 365 days/year × number of years of residence in the present hamlet + 50 μg/day × 365 days/year × number of years living in Cd non-polluted regions. In this formula, 333.5 g/day is the 1970 average daily intake of rice in this area, 34 µg/day is the Cd intake from foods other than rice in this area, and 50 μg/day is the average intake of Cd in non-polluted areas in Japan. Mortality risk ratios of LCd for all and specific causes were estimated after adjustments for age at baseline, smoking status, and history of hypertension using a Cox hazard model or Fine and Gray competing risks regression model.
The mortality risk ratios of LCd (+ 1 g) for all causes in women were significantly dose-dependently increased (risk ratio: 1.08). Relative risk of LCd for kidney and urinal tract disease, renal diseases, renal failure and toxic effects of cadmium were significantly higher in women.
The present study documents that individual LCd dose-dependently decreased life prognosis over long-term observation in women. LCd was significantly related to the increased mortality for renal disease and toxic effect of Cd in women. The result provides clear evidence that life prognosis was adversely affected by Cd-exposure, especially in women.
Priority Environmental Contaminants: Understanding Their Sources of Exposure, Biological Mechanisms, and Impacts on Health
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An estimated 23% of deaths worldwide are attributed to environmental causes. Moreover, environmental factors have a substantial adverse effect on children's health, contributing to an estimated 36% of childhood mortality. Due to the tremendous impact environment toxicants have on public health globally, it is important to understand their exposure sources, biological mechanisms of disease, and health impacts. This chapter provides an overview of the top 10, highest ranking environmental contaminants of concern as identified by the Agency for Toxic Substances and Disease Registry, four priority air pollutants, and seven contaminants of emerging concern. For each contaminant, or class of contaminants, the routes of exposure and health effects are described. Environmental contaminants are predicted to continue to substantially affect human health all over the world, rendering the study of environmental contaminants crucial to public health interventions.
Cadmium
2015, Handbook on the Toxicology of Metals: Fourth Edition
Cadmium (Cd) occurs naturally with zinc and lead in sulfide ores. Elevated concentrations in air, water, and soil may occur close to industrial emission sources, particularly those of nonferrous mining and metal refining industries. Cadmium metal has been used as an anticorrosive when electroplated onto steel. Cd compounds are used in batteries and as pigments. Cd is increasingly used in solar panels. Dispersive use of Cd is restricted by law in the European Union. Absorption of Cd compounds through the skin is negligible. Between 10% and 50% of inhaled Cd will be absorbed. Humans absorb 5-10% of ingested Cd. A low intake of calcium, zinc, or iron increases the degree of absorption. Cadmium is transported in plasma when bound to metallothionein (MT), a low molecular weight protein, and/or to certain high molecular weight proteins. The accumulation of Cd occurs in many tissues, with particularly long half-lives (10-30 years) in muscle, bone, kidney, and liver. MT-bound Cd in plasma is filtered through the renal glomeruli and reabsorbed in the tubuli, where the metal ion is released. When not all Cd is bound, toxic effects occur.
The average amount of Cd ingested in European and North American countries is 10-20 μg/day. The corresponding average urinary excretion is 0.5-1.0 μg/day and the blood concentration is 0.5-1.0 μg/L in nonsmokers; it is twice as high in smokers. The intake of Cd through food used to be higher in Japan than in Europe, but it has decreased and is currently similar to levels reported in European countries with high intakes.
Acute inhalation of Cd in air, for example from soldering or welding fumes, may lead to severe chemical pneumonitis. Long-term exposure to low air levels may lead to chronic obstructive lung disease and possibly to lung cancer. Long-term excessive exposure from the air or food leads to renal tubular dysfunction. The first sign of damage is low molecular weight proteinuria.
Long-term exposure from food, often combined with other means of delivery, may also lead to disturbance of calcium metabolism, osteoporosis, and osteomalacia, mainly among postmenopausal women. A disease exhibiting these features—called itai-itai disease—occurred in the 1950s in a Cd-polluted area of Japan: 124 cases were diagnosed up to 1970, and 196 cases in total were diagnosed up to 2011.
In laboratory animals, Cd has been shown to induce cancer of the lungs, prostate, and other organs. Epidemiological studies have found increased rates of cancer of the lungs and in some studies also in other organs. Cadmium is classified as a human carcinogen (Group 1) by the International Agency for Research on Cancer (IARC).
Exposure to Cd in the air at concentrations of 5-10 μg/m³ during a working life of 45 years may give rise to renal tubular dysfunction in a small proportion of exposed workers. At approximately 100 μg/m³, signs of chronic obstructive lung disease may develop. Epidemiological data shows that adverse kidney effects occur in sensitive occupational groups, as well as in general population groups, after lifelong exposures giving rise to urinary Cd (UCd) of 4 μg/g creatinine. At such exposures, bone effects including osteoporosis and increased risk of fractures may also occur in sensitive groups, mainly among postmenopausal women. Adverse bone and kidney effects may occur in a small but sensitive population group as a result of lifelong cadmium exposure with UCd of approximately 1 μg/g creatinine and higher, but the evidence is still inconclusive. Such exposure occurs in general population groups in many countries. There is no specific treatment for Cd poisoning. When there are signs of osteomalacia, large doses of vitamin D should be given. Because of the long half-life of Cd and the irreversibility of bone effects and some kidney effects primary prevention is essential.
The toxicological and environmental aspects of Cd have been reviewed in detail by Friberg et al., 1974, Friberg et al., 1985, Friberg et al., 1986, Tsuchiya, 1978, Nriagu, 1980, Nriagu, 1981, the WHO/IPCS (1992), the IARC, 1993, IARC., 2012, Järup et al., 1998c, the Agency for Toxic Substances and Disease Registry (ATSDR, 1999), Nordberg and Nordberg (2002), the European Union (EU, 2003, EU, 2007), Satarug and Moore (2004), and the World Health Organization (WHO) Food and Agriculture Organization (JECFA, 2004, JECFA., 2012), the European Food Safety Authority (EFSA, 2009, EFSA, 2012), and Akesson et al. (2014).
Cadmium accumulation in six common plant species associated with soils containing high geogenic cadmium concentrations at Le Gurnigel, Swiss Jura Mountains
2015, Catena
Citation Excerpt :
However, these concentrations are within the range of limit values of 5–10 mg·kg− 1 dry matter for plants and are lower than the critical values, which range from 10 to 20 mg·kg− 1 dry matter (Agence de l'Environnement et de la Maîtrise de l'Energie, 2010). It may be noted here that statistically significant toxic effects of Cd on humans are already signaled at levels as low as 0.3 mg·kg− 1, in the case of long-term exposure (e.g., in rice in east Asiatic countries; Ishihara et al., 2001; cf. also Satarug et al., 2003). It is expected that a rise in the concentration of Cd in a given soil would produce a stronger accumulation in a plant growing on it.
The uptake of cadmium (Cd) was analyzed for six different perennial plant species growing in a wooded pasture of the Swiss Jura Mountains, where the soils are geogenically enriched in Cd (4.58 mg·kg^− 1 on average (n = 36); maximal value: 16.3 mg·kg^− 1). The six selected plants — Hypericum maculatum (Hypericaceae), Alchemilla xanthochlora (Rosaceae), Cynosurus cristatus (Poaceae), Ranunculus acris (Ranunculaceae), Dactylis glomerata (Poaceae) and Acer pseudoplatanus (Sapindaceae) — show variable Cd contents among the species and among individuals from the same family (Poaceae). Average Cd concentrations in the selected plants are in the 2–6 mg·kg^− 1 range and exceed the maximal Cd concentration tolerated in vegetal feed for animals, which is established at 1 mg·kg^− 1. High Cd concentrations in the soil result in a reduction of Cd accumulation in the shoots and a corresponding increase in the roots. This implies that Cd transfer coefficients from the soil/rhizosphere to the plant are inversely proportional to the total Cd concentrations in soils and do not depend on plant species but instead on soil type. Sequential chemical extractions reveal that variations in Cd distribution between the bulk soil and the corresponding rhizospheric soil occur mainly in the Cd-bearing phases, which are exchangeable, bound to carbonates, and associated with organic matter. This is principally due to the incorporation of root exudates, which modify pH and redox conditions of the rhizosphere. Elevated Cd concentrations in the shoots of A. xanthochlora (up to 8 mg·kg^− 1), C. cristatus (9 mg·kg^− 1) and H. maculatum (3 mg·kg^− 1) may represent a long-term hazard for livestock and human health since these plants are used either by grazing cattle or for medicinal purposes. On the contrary, R. acris, A. pseudoplatanus, and especially D. glomerata show lower Cd concentrations and are of minor concern with regards to their environmental impact.

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Association between cadmium concentration in rice and mortality in the Jinzu River basin, Japan

Abstract

Introduction

Section snippets

Study population

Results

Discussion

Evaluation of qualitative and qualitative tests for proteinuria and glucosuria as screening tests for cadmium-induced renal tubular dysfunction

Jpn. J. Hyg.

Dose–response relationship between total cadmium intake and prevalence of renal dysfunction using general linear models

J. Appl. Toxicol.

Validity of cadmium concentration in rice as the ‘dose’ of the dose–response relationship between cadmium intake and renal dysfunction

Environ. Res.

Health effects of cadmium exposure — a review of the literature and a risk estimate

Scand. J. Work Environ. Health

Dose–response relationship between total cadmium intake and β2-microglobulinuria using logistic regression analysis

Toxicology

Dose–response relationship between dietary cadmium intake and metallothioneinuria in a population from a cadmium-polluted area of Japan

Toxicology

Dose–response relationship between dietary cadmium intake and metallothioneinuria using logistic regression analysis

Toxicology

High mortality and shortened life-span in patients with Itai-itai disease and subjects with suspected disease

Arch. Environ. Health

Dose–response relationship between total cadmium intake and β₂-microglobulinuria using logistic regression analysis